AB0323 DOES FRAILTY PREDICT METHOTREXATE DISCONTINUATION DUE TO ADVERSE EVENTS IN RHEUMATOID ARTHRITIS PATIENTS?
Authors: Y. Sobue, S. Asai, M. Suzuki, Y. Ohashi, S. Imagama
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) patients are more likely to develop frailty than general population [1]. Frailty is defined as the intermediate stages of health and disability in physical and cognitive function, and can lead to various negative health outcomes. On the other hand, Methotrexate (MTX) is an anchor disease-modifying antirheumatic drug. RA treatment has advanced significantly with the introduction of MTX. However, it was reported that 94.3% of MTX-naïve RA patients had adverse events (AEs) (C-OPERA study) [2]. Thus, RA patients on MTX should always be aware of complications and AEs. <h3>Objectives</h3> Since RA patients with frailty have more comorbidities than those with non-frailty, complications of RA or RA drugs are also expected to increase. The purpose of this study was to clarify whether frailty in RA patients influences the occurrence of AEs related to MTX. <h3>Methods</h3> Of 538 RA patients (an observational study, T-FLAG study) who visited us in 2020, 320 used MTX. After 2 years of follow-up, we investigated final follow-up date and AEs leading to MTX discontinuation. Frailty was defined as a score of 8 or more on the Kihon Checklist (KCL). Logistic regression analysis was performed to determine factors associated with MTX discontinuation due to AEs. MTX retention rates were calculated by Kaplan–Meier analysis, and crude retention rates were compared using the log-rank test. <h3>Results</h3> Of the 320 patients (249 females) in this study, 23 patients (7.2%) discontinued MTX due to AEs. AEs included liver disorder (26.1%), MTX pneumonia (21.7%), decreased renal function (13.0%). There were no patients with MTX discontinuation due to inefficacy. Mean age at baseline (standard deviation [SD]) was 68.2 (11.9)/ 64.5 (13.9) years (MTX discontinuation/ MTX continuation), MTX dose was 8.1 (2.8)/ 8.1 (2.9) mg, Clinical Disease Activity Index (CDAI) was 6.1 (6.1)/ 5.6 (7.3), KCL was 9.0 (5.0)/ 5.8 (4.0) point (p&lt;0.05), and the proportion of frailty was 56.5%/ 31.3% (p&lt;0.05). Logistic regression analysis revealed significant associations of MTX discontinuation with KCL (OR: 1.16, 95%CI: 1.06–1.28), and frailty (OR: 2.77, 95%CI: 1.16–6.61), adjusting for age and sex. The rate of MTX retention (at 1 year, and 2 years) was significantly lower in subjects with frailty (91.2%, and 86.6%) than in those with non-frailty (96.2%, and 95.1%) respectively. Comparing the patient characteristics at baseline in subjects with frailty and non-frailty, mean age, CDAI, KCL, and the proportion of MTX discontinuation due to AEs were significantly higher in subjects with frailty. <h3>Conclusion</h3> Our finding suggest that frailty was the significant factor of MTX discontinuation due to AEs, and the rate of MTX retention was significantly lower in the subjects with frailty compared to non-frailty. Moreover, the subjects with frailty had significantly higher mean age and disease activity, suggesting that frailty comprehensively reflects a bad condition. Frailty is significantly associated with poor physical function, and poorer physical function is reportedly associated with a poorer response to treatment [3]. Poor physical function (physical frailty) may make patients more prone to MTX discontinuation due to AEs. These findings suggest that frailty is a comprehensive index with high predictive power for MTX discontinuation due to AEs. Therefore, the occurrence of MTX AEs should be carefully monitored when using MTX in RA patients with frailty. <h3>References</h3> [1] Sobue Y, et al. Relationship between locomotive syndrome and frailty in rheumatoid arthritis patients by locomotive syndrome stage. Mod Rheumatol. 2021;32:546-53. [2] Atsumi T, et al. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Ann Rheum Dis. 2016;75(1):75-83. [3] Anderson JJ, et al. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000;43:22-9. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.